This is a blinded, placebo-controlled study to evaluate the role of genetic factors in response to standard smoking cessation treatment, to evaluate the role of genetic factors in response to bupropion treatment, and to evaluate the psychobiological mechanisms by which genotype and bupropion influence smoking cessation. About 700 subjects will be randomized to either bupropion or placebo. They will have a blood draw for genotyping, and receive group smoking cessation counseling. Subjects will be interviewed by phone at 6 and 12 months post treatment. Subsequent statistical analysis will determine whether outcome (successful cessation) is influenced by bupropion vs placebo, and by genetic predisposition vs protection, based on the SLC6A3-9 alleles. Multivariate analysis will also account for screening/covariates (demographics, history/physical, depression, personality, smoking urges), mediating variables (reinforcing nicotine levels, mood, withdrawal, cravings), and treatment variables (adherence, side effects, expectations).